Experiments are being conducted to obtain detailed understanding of neurotransmitter, hormone and drug actions involving cyclic nucleotides in the nervous system. Two forms of adenylate cyclase have recently been identified in brain. Differential responses to neuroleptic drugs, F anion, GTP, Ca 2 ion and a calcium-dependent regulatory protein will be analyzed further. The possible participation of these factors in receptor-cyclase coupling is being examined. A second series of experiments is designed to better understand the regulation by cyclic AMP of guanylate cyclase activity in C-6 astrocytoma cells. Finally the pre-junctional role of cyclic nucleotides at a giant-fiber synapse will be analyzed with electrophysiological techniques. BIBLIOGRAPHIC REFERENCES: Brostrom, M.A., Brostrom, C.O., Breckenridge, B. McL., Wolff, D.J., Regulation of adenylate cyclase from glial tumor cells by calcium and a calcium-binding protein. J. Biol. Chem. 251, 4744-4750 (1976). Brostrom, M.A., Calcium-dependent regulation of brain adenylate cyclase. Adv. Cyclic Nucleotide Research, Vol. 9, 1978, in press.